The FREEDOM (Frequent Dialysis Outcomes & Markers) Study is a randomized clinical trial designed to test hypotheses related to the feasibility, safety, and efficacy of frequent (>3 times per week) hemodialysis. The recently completed NIDDK-funded HEMO Study demonstrated that survival and many other outcomes were not appreciably influenced by significant increases in equilibrated Kt/Vurea, a parameter of dialysis dose, when hemodialysis was given thrice weekly. Clinical experience and published anecdotal reports suggest that more frequent dialysis may result in reduced frequency and duration of hospitalization, improved control of volume overload, hypertension and anemia, correction of disorders of mineral metabolism, and enhanced quality of life. Given the high mortality rates and significant morbidity associated with end-stage renal disease, a rigorous evaluation of alternative dialysis strategies is warranted. The Investigators have constructed a consortium of University- and community-based nephrologists and dialysis units throughout the state of California - the California Coordinating Clinical Center (CCC). We serve urban and suburban communities with extensive racial, ethnic and socioeconomic diversity. We intend on enrolling 200 subjects {adults and children) as requested by the RFA with a "recruit to replace" strategy to maximize the information gained and resources utilized. Subjects will be randomized in a 1:1:1:1 ratio to hemodialysis three, four, five, or six days per week, with dialysis efficiency targets kept equivalent on a per treatment basis. We will work closely with the General Clinical Research Centers at UCSF, UCLA, and UC San Diego. The sample size will not be sufficient to demonstrate a difference in survival among groups. However, the study should have sufficient power to detect significant differences in several of the planned safety and efficacy outcomes and measures. The California CCC Investigators and Consultants have considerable expertise in many of the selected outcomes and measures, including vascular access, nutritional status, vascular calcification, inflammation and oxidative stress, physical function, cognitive function, quality of life, depression, mineral metabolism, bone density and dynamics, anemia, and dialysis dose quantification. We are committed to working cooperatively and constructively with the other CCC and Data Analysis Coordinating Center-regardless of the final agreed-upon protocol.